Italian Guidelines for the Management of Sporadic Primary Hyperparathyroidism.

AIM: This guideline (GL) is aimed at providing a clinical practice reference for the management of sporadic primary hyperparathyroidism (PHPT) in adults. PHPT management in pregnancy was not considered. METHODS: This GL has been developed following the methods described in the Manual of the Italian National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinology (AME) and Società Italiana dell'Osteoporosi, del Metabolismo Minerale e delle Malattie dello Scheletro (SIOMMMS) identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence. Those classified as "critical" were considered for the clinical practice recommendations. RESULTS: The present GL provides recommendations about the roles of pharmacological and surgical treatment for the clinical management of sporadic PHPT. Parathyroidectomy is recommended in comparison to surveillance or pharmacologic treatment in any adult (outside of pregnancy) or elderly subject diagnosed with sporadic PHPT who is symptomatic or meets any of the following criteria: • Serum calcium levels >1 mg/dL above the upper limit of normal range. • Urinary calcium levels >4 mg/kg/day. • Osteoporosis disclosed by DXA examination and/or any fragility fracture. • Renal function impairment (eGFR <60 mL/min). • Clinic or silent nephrolithiasis. • Age ≤50 years. Monitoring and treatment of any comorbidity or complication of PHPT at bone, kidney, or cardiovascular level are suggested for patients who do not meet the criteria for surgery or are not operated on for any reason. Sixteen indications for good clinical practice are provided in addition to the recommendations. CONCLUSION: The present GL is directed to endocrinologists and surgeons - working in hospitals, territorial services or private practice - and to general practitioners and patients. The recommendations should also consider the patient's preferences and the available resources and expertise.

Parathyroid Retrospective Analysis of Neoplasms Incidence (pTRANI Study): An Italian Multicenter Study on Parathyroid Carcinoma and Atypical Parathyroid Tumour.

BACKGROUND: Parathyroid cancer (PC) is a rare sporadic or hereditary malignancy whose histologic features were redefined with the 2022 WHO classification. A total of 24 Italian institutions designed this multicenter study to specify PC incidence, describe its clinical, functional, and imaging characteristics and improve its differentiation from the atypical parathyroid tumour (APT). METHODS: All relevant information was collected about PC and APT patients treated between 2009 and 2021. RESULTS: Among 8361 parathyroidectomies, 351 patients (mean age 59.0 ± 14.5; F = 210, 59.8%) were divided into the APT (n = 226, 2.8%) and PC group (n = 125, 1.5%). PC showed significantly higher rates (p < 0.05) of bone involvement, abdominal, and neurological symptoms than APT (48.8% vs. 35.0%, 17.6% vs. 7.1%, 13.6% vs. 5.3%, respectively). Ultrasound (US) diameter >3 cm (30.9% vs. 19.3%, p = 0.049) was significantly more common in the PC. A significantly higher frequency of local recurrences was observed in the PC (8.0% vs. 2.7%, p = 0.022). Mortality due to consequences of cancer or uncontrolled hyperparathyroidism was 3.3%. CONCLUSIONS: Symptomatic hyperparathyroidism, high PTH and albumin-corrected serum calcium values, and a US diameter >3 cm may be considered features differentiating PC from APT. 2022 WHO criteria did not impact the diagnosis.

A Prospective Multicenter Study Examining the Relationship Between Thyroid Cancer Treatment Outcomes and the Presence of Autoimmune Thyroiditis.

Background: There is some controversy on the potential relationship between autoimmune processes and clinicopathologic features as well as prognosis of differentiated thyroid cancer (DTC), and the evidence is limited by its largely retrospective nature. We examined the relationship between the presence of autoimmune thyroiditis (AT) and 1-year thyroid cancer treatment outcomes in a large multicenter study using prospectively collected data. Methods: We included data from consecutive DTC patients enrolled in the Italian Thyroid Cancer Observatory (ITCO) database (NCT04031339). We divided the groups according to the presence (AT) or absence (no autoimmune thyroiditis [noAT]) of associated AT. We used propensity score matching to compare the clinical features and outcomes between the two groups at 1-year follow-up. Results: We included data from 4233 DTC patients, including 3172 (75%) females. The American Thyroid Association (ATA) risk levels were as follows: 51% (2160/4233) low risk, 41.3% (1750/4233) intermediate risk, and 7.6% (323/4233) high risk. There were 1552 patients (36.7%) who had AT. Before propensity score matching, AT patients were significantly younger and had a smaller and bilateral tumor (p < 0.0001). Patients with AT more frequently fell into the low- and intermediate-risk categories, while the ATA high risk was more frequent among noAT patients (p = 0.004). After propensity score matching, patients with AT more frequently showed evidence of disease (structural/biochemical incomplete response) versus excellent/indeterminate response, compared with patients without AT (7.3% vs. 4.5%, p = 0.001), with an odds ratio of 1.86 ([confidence interval: 1.3-2.6], p = 0.0001). However, when considering only structural persistence as the outcome, no statistically significant differences were observed between patients with or without AT (3.4% vs. 2.7%, p = 0.35). The elevated risk associated with the ATA intermediate and high risk at diagnosis remained consistently statistically significant. Conclusions: In this large prospective series, biochemical persistence was more frequent, at 1-year follow-up, in AT patients. However, there was no significant association between the presence of AT and structural persistence of disease. These findings may be explained by the presence of a residual thyroid tissue.

Updates from Our Institutional Experience with Thyroid Nodules Diagnosed as Metastases.

BACKGROUND: Thyroid metastases (TMs) are a rare entity, ranging between 0 and 24% in the autopsy series. In the assessment of the best management, the discrimination between a primary and a metastatic thyroid lesion is crucial. In this regard, fine needle aspiration cytology (FNAC) is likely to play a crucial role especially when ancillary techniques (i.e., immunocytochemistry (ICC) and molecular testing) are carried out. METHODS: We searched for all the TMs diagnosed using FNAC and analyzed between 2014 and 2023. The cases were processed with liquid-based (LBC) and ICC and molecular testing performed on LBC-stored material. RESULTS: We reported 2.2% (19 cases) of TMs out of 1022 malignancies. TMs included: 1 larynx carcinoma (LX-Ca), 1 melanoma, 2 breast carcinomas (B-Ca), 3 lung carcinomas (LG-Ca), 4 gastro-intestinal carcinomas (GI-Ca), and 8 clear cell renal carcinomas (CCRC). All patients had a previous cancer history, between 300 and 2 months from the primary cancers. The morphological features were supported by ICC, which were contributive in 100% of cases. All TMs cases were characterized by multiple thyroid nodules except the melanoma case. Four cases underwent total thyroidectomy (1 B, 1 LX, 1 melanoma, and 1 CCRC) whilst 15 TMs were treated with radio-chemotherapy. CONCLUSIONS: FNAC empowered the diagnostic workup of patients with TMs avoiding useless surgery. The low sensitivity of cytology might be reinforced by the application of ancillary techniques. We found a predominant rate of kidney metastatic carcinomas, followed by lung and breast. TMs are frequently multifocal and in a context of a systemic disease so a tailored therapy seems to be the best treatment.

Diagnostic role of FNA cytology in the evaluation of cervical lymph nodes in thyroid cancers: Combined evaluation of thyroglobulin in eluate from FNA cytology.

BACKGROUND: The presurgical evaluation of cervical lymph nodes (CLNs) in the management of thyroid malignant lesions is crucial for the extent of surgery or detection of metastases. In these last decades, fine-needle aspiration cytology (FNAC) has been shown to have a central role in the detection of nodal thyroid metastases. It is adopted for the possibility of confirming suspected metastases either in the presurgical phase or in the follow-up of patients after thyroidectomy. However, FNAC from CLNs can be challenging, especially in cystic lesions. In this regard, the combination of FNAC with thyroglobulin measurement in the eluate from FNAC (Tg-FNAC) seems to increase the sensitivity of FNAC in the detection of CLN metastases. The role of FNAC and Tg-FNAC was investigated in this series. METHODS: One hundred fifty-three prospective cytological samples of CLNs were studied along with surgical follow-up in the period between 2020 and 2022. Immunocytochemistry (ICC) was performed on liquid-based cytology-stored material. RESULTS: One hundred fifty-nine enlarged CLNs included 19 central lymph nodes and 140 CLNs. Forty-two thyroidal CLN metastases and 117 reactive lymph nodes were found. Thirty-one CLN dissections were performed in patients with a previous diagnosis of thyroid carcinoma (mostly papillary thyroid carcinoma [PTC]), whereas 128 CLNs with a concomitant suspicious and/or malignant thyroid nodule were found. There was one false-positive case among all the malignant histologically confirmed cases, and two of 117 reactive CLNs (1.7%) had a diagnosis of metastatic PTC. Markedly high Tg-FNAC was found in all metastatic CLNs, including 11 cystic metastatic CLNs detected by Tg-FNAC with a negative FNAC. ICC (including Tg, CK-19, and LCA) recognized nine cases with low Tg-FNAC and scant suspicious thyrocytes. Tg-FNAC plus FNAC diagnosed 94.2% of malignancies. CONCLUSIONS: FNAC represents a valid method for the evaluation of CLNs, especially combined with ICC. Tg-FNAC is an additional method with a useful role in FNAC.

p53 expression in cytology samples may represent a marker of early-stage cancer.

BACKGROUND: TP53 gene plays a major role in the negative control of cell proliferation and in the regulation of signaling cascades. TP53 mutation may have a relevant role in the malignant transformation of thyroid cells as well as thyroid tumor progression. TP53 mutation has been detected only in few well differentiated thyroid carcinomas and is absent in benign conditions. METHODS: A total of 162 prospective thyroid cytology and corresponding histological samples diagnosed from atypia of indeterminate significance (AUS) to malignant, were studied via immunocytochemistry for p53. Hence, 50 benign lesions (B) were used as negative control. Molecular analysis for p53 only was performed. RESULTS: The cytology resulted in 50 B, 48 AUS, 40 follicular neoplasms (FNs), 23 suspicious for malignancy (SFM), and 1 malignant (M) case. The authors reported 102 negative and 60 positive p53 cases. The 60 positive cases included 27 cases with weak and/or focal cytoplasmic positivity (+1) and 33 with cases moderate (2+) to strong (3+) cytoplasmic and/or nuclear expression. Overall, 71 cases had histology (2 B, 11 AUS, 37 FN, 20 SFM, and 1 M) including 61.7% benign and 38.2% malignant diagnoses. Only 16 of 71 (5 FN, 10 SFM, and 1 M) were p53-positive. Furthermore, 100% AUS and 86.5% FN cases were p53-negative, none of which had malignant histology. All p53-positive cases were associated with a larger nodule size, tall-cell variant subtype, multifocality, extra thyroidal infiltration, and nodal metastases. Noninvasive follicular thyroid neoplasm with papillary like nuclear features were negative for p53. Few discrepancies in p53 intensity were observed on histology; there were no differences with the molecular testing. CONCLUSIONS: p53 might be useful in discriminating thyroid follicular lesions. p53 is likely to be a useful diagnostic marker in recognizing indeterminate lesions that are well-differentiated thyroid cancers.

Italian Guidelines for the Management of Non-Functioning Benign and Locally Symptomatic Thyroid Nodules.

AIM: This guideline (GL) is aimed at providing a reference for the management of non-functioning, benign thyroid nodules causing local symptoms in adults outside of pregnancy. METHODS: This GL has been developed following the methods described in the Manual of the National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinology (AME) identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence and only those classified as "critical" were considered in the formulation of recommendations. RESULTS: The present GL contains recommendations about the respective roles of surgery and minimally invasive treatments for the management of benign symptomatic thyroid nodules. We suggest hemithyroidectomy plus isthmectomy as the first-choice surgical treatment, provided that clinically significant disease is not present in the contralateral thyroid lobe. Total thyroidectomy should be considered for patients with clinically significant disease in the contralateral thyroid lobe. We suggest considering thermo-ablation as an alternative option to surgery for patients with a symptomatic, solid, benign, single, or dominant thyroid nodule. These recommendations apply to outpatients, either in primary care or when referred to specialists. CONCLUSION: The present GL is directed to endocrinologists, surgeons, and interventional radiologists working in hospitals, in territorial services, or private practice, general practitioners, and patients. The available data suggest that the implementation of this GL recommendations will result in the progressive reduction of surgical procedures for benign thyroid nodular disease, with a decreased number of admissions to surgical departments for non-malignant conditions and more rapid access to patients with thyroid cancer. Importantly, a reduction of indirect costs due to long-term replacement therapy and the management of surgical complications may also be speculated.

Update regarding the role of PD-L1 in oncocytic thyroid lesions on cytological samples.

AIMS: Several papers have shown that programmed death-ligand 1 (PD-L1) expression is a relevant predictive biomarker in anti-PD-L1 cancer immunotherapy. While its role in several human cancers is correlated with poor prognosis and resistance to anticancer therapies, in thyroid cancers the role of PD-L1 remains questionable. Few articles have studied PD-L1 in thyroid fine-needle aspiration cytology (FNAC), demonstrating a possible correlation with papillary thyroid carcinoma. However, its role in oncocytic thyroid lesions remains controversial. We accordingly examine the performance of PD-L1 immunostaining in liquid based cytology (LBC) from oncocytic lesions. METHODS: From January 2019 to March 2021, 114 thyroid lesions diagnosed by FNAC from lesions with a predominant oncocytic component, were enrolled for evaluation by PD-L1 immunostaining on both LBC and corresponding histology samples. RESULTS: The FNAC cohort included 51 benign (B, negative controls), 4 atypia of undetermined significance/follicular lesions of undetermined significance (AUS/FLUS), 57 follicular lesions (follicular neoplasm/suspicious for FN, FN/SFN) and 2 suspicious for malignancy (SFM) cases. Fifty-four cases (11B, 2 AUS/FLUS, 39 FN/SFN and 2 SFM) had histological follow-up including: 1B case resulted as a hyperplastic oxyphilic nodule in Hashimoto thyroiditis (HT), 10B as goitre, 2 AUS/FLUS cases as oncocytic adenomas (OAs); 39 FN/SFN included 27 OAs, 4 FA and 8 oncocytic follicular carcinoma (OFC). The two SFM cases were diagnosed on histopathology as OAs. Increased plasma membrane and cytoplasmic PD-L1 expression were found in 47 cases of the LBC cases (41.2%). Among the histological series, 67.3% of OAs and 75% of OFC had PD-L1 expression, while negative PD-L1 was found in hyperplastic oncocytic cells in HT. A positivity in more than 30% of the neoplastic cells was found in 72.9% of the cases including six OFC. CONCLUSIONS: These data suggest that PD-L1 expression is expressed in oncocytic thyroid lesions. While weak PD-L1 expression failed to discriminate benign from malignant lesions, OFC demonstrated more intense cytoplasmic and membranous expression.

Long-Term Adherence to Levothyroxine Replacement Therapy in Thyroidectomized Patients.

(1) Background: We evaluated the long term adherence to two distinct formulations of levothyroxine (L-T4), liquid or solid, which are differently influenced by concomitant food ingestion. (2) Methods: A total of 106 thyroidectomized patients (82 female, mean age 58.2 ± 13.3 years) on L-T4 replacement therapy in either liquid (n = 52) or solid formulation (n = 54) were administered the four-item Medication Adherence Questionnaire (MAQ). (3) Results: The study population had 59.4% adherers and 40.6% non-adherers. The global MAQ score was significantly better in patients under liquid L-T4 in comparison to those under solid L-T4 (0.42 ± 0.82 vs. 0.83 ± 0.95, respectively, p = 0.0085). The patients on tablet L-T4 forgot to take their medication more frequently than those on liquid LT4 treatment (p = 0.0159) and were more often careless at times about taking their medication (p = 0.007), whilst about one in two thyroidectomized patients preferred tablets for lifetime medication therapy. The global MAQ score was directly correlated with the circulating TSH levels in the whole study population (0.700, p < 0.0001) and inversely correlated with both the FT3 (−0.220, p = 0.0232) and FT4 (−0.327, p = 0.0006) serum concentrations. (4) Conclusions: Long-term adherence to L-T4 treatment was globally satisfactory although it was better for the liquid formulation, which appears to represent an easier-to-manage L-T4 replacement therapy for most thyroidectomized patients, particularly for those with difficulties in taking L-T4 while fasting.

Misdiagnosed giant parathyroid cyst: differential diagnosis of a neck mass of the central region.

Parathyroid cysts (PCs) are rare benign lesions representing between the 0.08% and the 0.34% of the neck masses going on surgery. They should be considered in the differential diagnosis of neck masses, especially in the differential diagnosis of the cystic anterior neck masses.Approximately 300 cases of PC are reported within the international literature.The gold standard for diagnosis is the evidence of high-level intact parathyroid hormone in cystic fluid. It is important to diagnose PCs before surgery, not intraoperatively, in order to avoid unnecessary surgeries or superfluous excision of part of the thyroid gland and prevent the patient from iatrogenic hypothyroidism.A surgical approach is required in those patients with large-sized cysts, relapses despite needle aspirations or if it causes hyperparathyroidism.We describe a case report of a patient, initially misdiagnosed with a thyroid cyst swelling, who instead had a giant non-functioning PC, which produced dyspnoea or dysphagia.

Does Locally Advanced Thyroid Cancer Have Different Features? Results from a Single Academic Center.

BACKGROUND: Despite the fact that the majority of thyroid cancers are indolent, 15% of patients with well-differentiated carcinoma including papillary thyroid carcinoma (PTC) present with locally advanced thyroid cancer (LATC) at diagnosis. The current study analyzes a cohort of patients with LATC focusing on their risk for local recurrence, distant metastases, and overall survival. MATERIALS AND METHODS: From January 2010 to December 2020, 65 patients with LATC were retrieved, including 42 cases with preoperative cytological samples. BRAFV600E and TERT mutations were performed on both cytology and histopathology specimens in this cohort. RESULTS: Among the 65 cases, 42 (65%) were women. The median age was 60.1 years. Histological diagnoses included 25 (38.4%) with classic PTC and 30 (46.1%) aggressive variants of PTC, mostly tall cell variant (17 cases, 26.1%). Multifocality was seen in 33 cases (50.8%). All patients had nodal metastases. The most common site of extrathyroidal extension was the recurrent laryngeal nerve (69.2%). Staging revealed 21 cases were stage I, none were stage II, 33 were stage III, and 7 were stage IVa and 4 stage IVb. No differences were found between well and poorly/undifferentiated thyroid cancers. CONCLUSION: These data suggest that locally advanced thyroid cancers, including variants of PTC, exhibit a more aggressive biological course and should accordingly be more assertively managed.

Radiofrequency ablation and related ultrasound-guided ablation technologies for treatment of benign and malignant thyroid disease: An international multidisciplinary consensus statement of the American Head and Neck Society Endocrine Surgery Section with the Asia Pacific Society of Thyroid Surgery, Associazione Medici Endocrinologi, British Association of Endocrine and Thyroid Surgeons, European Thyroid Association, Italian Society of Endocrine Surgery Units, Korean Society of Thyroid Radiology, Latin American Thyroid Society, and Thyroid Nodules Therapies Association.

BACKGROUND: The use of ultrasound-guided ablation procedures to treat both benign and malignant thyroid conditions is gaining increasing interest. This document has been developed as an international interdisciplinary evidence-based statement with a primary focus on radiofrequency ablation and is intended to serve as a manual for best practice application of ablation technologies. METHODS: A comprehensive literature review was conducted to guide statement development and generation of best practice recommendations. Modified Delphi method was applied to assess whether statements met consensus among the entire author panel. RESULTS: A review of the current state of ultrasound-guided ablation procedures for the treatment of benign and malignant thyroid conditions is presented. Eighteen best practice recommendations in topic areas of preprocedural evaluation, technique, postprocedural management, efficacy, potential complications, and implementation are provided. CONCLUSIONS: As ultrasound-guided ablation procedures are increasingly utilized in benign and malignant thyroid disease, evidence-based and thoughtful application of best practices is warranted.

Minimal Extrathyroidal Extension in Predicting 1-Year Outcomes: A Longitudinal Multicenter Study of Low-to-Intermediate-Risk Papillary Thyroid Carcinoma (ITCO#4).

Background: The role of minimal extrathyroidal extension (mETE) as a risk factor for persistent papillary thyroid carcinoma (PTC) is still debated. The aims of this study were to assess the clinical impact of mETE as a predictor of worse initial treatment response in PTC patients and to verify the impact of radioiodine therapy after surgery in patients with mETE. Methods: We reviewed all records in the Italian Thyroid Cancer Observatory database and selected 2237 consecutive patients with PTC who satisfied the inclusion criteria (PTC with no lymph node metastases and at least 1 year of follow-up). For each case, we considered initial surgery, histological variant of PTC, tumor diameter, recurrence risk class according to the American Thyroid Association (ATA) risk stratification system, use of radioiodine therapy, and initial therapy response, as suggested by ATA guidelines. Results: At 1-year follow-up, 1831 patients (81.8%) had an excellent response, 296 (13.2%) had an indeterminate response, 55 (2.5%) had a biochemical incomplete response, and 55 (2.5%) had a structural incomplete response. Statistical analysis suggested that mETE (odds ratio [OR] 1.16, p = 0.65), tumor size >2 cm (OR 1.45, p = 0.34), aggressive PTC histology (OR 0.55, p = 0.15), and age at diagnosis (OR 0.90, p = 0.32) were not significant risk factors for a worse initial therapy response. When evaluating the combination of mETE, tumor size, and aggressive PTC histology, the presence of mETE with a >2 cm tumor was significantly associated with a worse outcome (OR 5.27 [95% confidence interval], p = 0.014). The role of radioiodine ablation in patients with mETE was also evaluated. When considering radioiodine treatment, propensity score-based matching was performed, and no significant differences were found between treated and nontreated patients (p = 0.24). Conclusions: This study failed to show the prognostic value of mETE in predicting initial therapy response in a large cohort of PTC patients without lymph node metastases. The study suggests that the combination of tumor diameter and mETE can be used as a reliable prognostic factor for persistence and could be easily applied in clinical practice to manage PTC patients with low-to-intermediate risk of recurrent/persistent disease.

Thyroid Cancer: Toward Surgical Evolution.

It has been more than five years since the American Thyroid Association (ATA) and the Italian consensus on thyroid cancer was published [...].

The Role of Cytology in the Diagnosis of Subcentimeter Thyroid Lesions.

Thyroid nodules are common and typically detected by palpation and/or ultrasound (US). Guidelines have defined the management of large nodules, but controversy exists regarding nodules ≤ 1 cm. We evaluated a cohort of patients with subcentimeter nodules to determine their rate of malignancy (ROM). A total of 475 thyroid FNAs of lesions ≤ 1 cm with available follow-up were identified from January 2015-December 2019. For comparative analysis, we added a control series of 606 thyroid lesions larger than 1 cm from the same reference period. All aspirates were processed with liquid-based cytology and classified according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). Subcentimeter nodules were stratified as 35 category I-non-diagnostic cases (ND; 7.3%), 144 category II-benign lesions (BL; 30.3%), 12 category III-atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS; 2.5%), 12 category IV-follicular neoplasm/suspicious for follicular neoplasm (FN/SFN; 2.5%), 124 category V-suspicious for malignancy (SM; 26.1%), and 148 category VI-positive for malignancy (PM; 31.1%). A total of 307 cases (64.6%) underwent subsequent surgery. Only one ND and three BLs had a malignant outcome. ROM for indeterminate lesions (III + IV) was 3.2%; with 1.6% for category III and 3.2% for category IV. ROM for the malignant categories (V + VI) was 88.2%. The control cohort of lesions demonstrated a higher number of benign histological diagnoses (67.3%). We documented that 57.2% of suspected subcentimeter lesions were malignant, with a minor proportion that belonged in indeterminate categories. There were very few ND samples, suggesting that aspirates of subcentimeter lesions yield satisfactory results. Suspected US features in subcentimeter lesions should be evaluated and followed by an interdisciplinary team for appropriate patient management.

American Association of Clinical Endocrinology And Associazione Medici Endocrinologi Thyroid Nodule Algorithmic Tool.

OBJECTIVE: The first edition of the American Association of Clinical Endocrinology/American College of Endocrinology/Associazione Medici Endocrinologi Guidelines for the Diagnosis and Management of Thyroid Nodules was published in 2006 and updated in 2010 and 2016. The American Association of Clinical Endocrinology/American College of Endocrinology/Associazione Medici Endocrinologi multidisciplinary thyroid nodules task force was charged with developing a novel interactive electronic algorithmic tool to evaluate thyroid nodules. METHODS: The Thyroid Nodule App (termed TNAPP) was based on the updated 2016 clinical practice guideline recommendations while incorporating recent scientific evidence and avoiding unnecessary diagnostic procedures and surgical overtreatment. This manuscript describes the algorithmic tool development, its data requirements, and its basis for decision making. It provides links to the web-based algorithmic tool and a tutorial. RESULTS: TNAPP and TI-RADS were cross-checked on 95 thyroid nodules with histology-proven diagnoses. CONCLUSION: TNAPP is a novel interactive web-based tool that uses clinical, imaging, cytologic, and molecular marker data to guide clinical decision making to evaluate and manage thyroid nodules. It may be used as a heuristic tool for evaluating and managing patients with thyroid nodules. It can be adapted to create registries for solo practices, large multispecialty delivery systems, regional and national databases, and research consortiums. Prospective studies are underway to validate TNAPP to determine how it compares with other ultrasound-based classification systems and whether it can improve the care of patients with clinically significant thyroid nodules while reducing the substantial burden incurred by those who do not benefit from further evaluation and treatment.

How limited molecular testing can also offer diagnostic and prognostic evaluation of thyroid nodules processed with liquid-based cytology: Role of TERT promoter and BRAF V600E mutation analysis.

BACKGROUND: Mutational analysis contributes to the diagnosis and prognosis of thyroid nodules analyzed with fine-needle aspiration cytology (FNAC). Although several advanced molecular tests based on multiple molecular markers are available for clinical use and have increased their impact on clinical management of patients, they are not widely available. Among them is BRAF V600E, one of the most studied mutations. Other genetic alterations, such as TERT promoter mutations, may coexist in thyroid carcinomas. Previous studies have demonstrated that this duet might be involved in the aggressiveness of thyroid cancer, although its prognostic value related to mortality remains undefined. The detection of such genetic alterations in thyroid liquid-based cytology (LBC) thus may assist with patient management. METHODS: From January 2013 to June 2014, 356 thyroid FNAC samples were processed by LBC, including 174 surgical follow-up samples. BRAF V600E and TERT mutation analyses were performed on both LBC and histopathology. RESULTS: The study included 119 samples categorized as atypia of undetermined significance, 42 categorized as follicular neoplasms, 61 categorized as suspicious for malignancy, and 34 categorized as positive for malignancy. BRAF V600E mutation was detected in 10.4% of all cases, whereas TERT promoter mutations were identified in 1.1%. TERT-mutated cases belonged to the positive for malignancy category, with a histologic diagnosis of tall cell variant of papillary thyroid carcinoma. These genetic alterations correlated with lymph node metastases (P = .0349) and higher disease stage. CONCLUSIONS: BRAF V600E and TERT analysis can be performed on LBC. TERT mutations are rarely identified in well differentiated thyroid carcinoma but are associated with higher stage. Although a larger molecular panel may offer more information, analyzing these few point mutations is still likely to be useful for managing potentially more aggressive thyroid carcinomas.

The THYCOVIT (Thyroid Surgery during COVID-19 pandemic in Italy) study: results from a nationwide, multicentric, case-controlled study.

The outbreak of the COVID-19 pandemic has led to a disruption of surgical care. The aim of this multi-centric, retrospective study was to evaluate the impact of the pandemic on surgical activity for thyroid disease among the Italian Units of Endocrine Surgery. Three phases of the pandemic were identified based on the epidemiological situation and the public measures adopted from the Italian Government (1st phase: from 9th March to 3rd May 2020; 2nd phase: from 4th May to 14th June; 3rd phase: from 15th June to 31st). The patients operated upon during these phases were compared to those who underwent surgery during the same period of the previous year. Overall, 3892 patients from 28 Italian endocrine surgical units were included in the study, 1478 (38%) operated upon during COVID-19 pandemic, and 2414 (62%) during the corresponding period of 2019. The decrease in the number of operations was by 64.8%, 44.7% and 5.1% during the three phases of COVID-19 pandemic, compared to 2019, respectively. During the first and the second phases, the surgical activity was dedicated mainly to oncological patients. No differences in post-operative complications were noted between the two periods. Oncological activity for thyroid cancer was adequately maintained during the COVID-19 pandemic.

Neck complaints before and after uncomplicated thyroidectomy: prevalence, postoperative outcome and relationships with thyroid weight and reflux like symptoms.

PURPOSE: The surgical thyroid disease includes upper aerodigestive complaints with not homogenous prevalence and specific features. The purpose was to analyze before and after total thyroidectomy (TT) the prevalence and severity of voice, swallowing, respiratory, and reflux airway symptoms in relation with thyroid weight. METHODS: A total of 98 consenting patients undergoing TT were enrolled. Preoperatively, 1 and 3 months after TT, patients underwent videolaryngoscopy, subjective evaluation of voice (VIS), swallowing (SIS and EAT-10), respiratory (mMRC), and reflux symptoms (RSI, Gerd-Q). The scores were analyzed based on thyroid weight (<25 gr, 26-50 gr, 51-75 gr, >75 gr) and post-operative score gain was calculated from the score before TT and the follow-up examination. RESULTS: In total, 40/98 selected cases of uncomplicated TT completed the postoperative evaluation. Endoscopic signs suggestive of reflux disease were observed in 1/40 (2.5%) and 0/19 cases before and after TT respectively. The prevalence of cases with abnormal reflux symptom index decreased significantly after surgery (8/40 vs 1/40) (p < 0.05), similarly occurred for the Gerd-Q (4/40 vs 1/40) (p < 0.05). Three months after TT the voice, swallowing and respiratory scores were significantly lower than the preoperative ones (p < 0.05). The SIS correlated positively with EAT-10 and RSI. After 3 months the postoperative score gain of voice, swallowing, respiratory, and reflux symptoms (Gerd-Q) was statistically higher (p < 0.05) in the cases with heaviest gland. CONCLUSIONS: The surgical thyroid disease is associated to mild aerodigestive preoperative compressive symptoms, that include respiratory abnormalities and reflux like symptoms, regardless of the gland weight. In absence of endoscopic signs of airway reflux the presence of reflux symptoms suggests an overlapping with thyroid neck complaints. The patients undergoing uncomplicated TT had improvement in compressive symptoms and the greatest improvement is seen in larger goiters.

Real-World Performance of the American Thyroid Association Risk Estimates in Predicting 1-Year Differentiated Thyroid Cancer Outcomes: A Prospective Multicenter Study of 2000 Patients.

Background: One of the most widely used risk stratification systems for estimating individual patients' risk of persistent or recurrent differentiated thyroid cancer (DTC) is the American Thyroid Association (ATA) guidelines. The 2015 ATA version, which has increased the number of patients considered at low or intermediate risk, has been validated in several retrospective, single-center studies. The aims of this study were to evaluate the real-world performance of the 2015 ATA risk stratification system in predicting the response to treatment 12 months after the initial treatment and to determine the extent to which this performance is affected by the treatment center in which it is used. Methods: A prospective cohort of DTC patients collected by the Italian Thyroid Cancer Observatory web-based database was analyzed. We reviewed all records present in the database and selected consecutive cases that satisfied inclusion criteria: (i) histological diagnosis of DTC, with the exclusion of noninvasive follicular thyroid neoplasm with papillary-like nuclear features; (ii) complete data of the initial treatment and pathological features; and (iii) results of 1-year follow-up visit (6-18 months after the initial treatment), including all data needed to classify the estimated response to treatment. Results: The final cohort was composed of 2071 patients from 40 centers. The ATA risk of persistent/recurrent disease was classified as low in 1109 patients (53.6%), intermediate in 796 (38.4%), and high in 166 (8.0%). Structural incomplete responses were documented in only 86 (4.2%) patients: 1.5% in the low-risk, 5.7% in the intermediate-risk, and 14.5% in the high-risk group. The baseline ATA risk class proved to be a significant predictor of structural persistent disease, both for intermediate-risk (odds ratio [OR] 4.67; 95% confidence interval [CI] 2.59-8.43) and high-risk groups (OR 16.48; CI 7.87-34.5). Individual center did not significantly influence the prediction of the 1-year disease status. Conclusions: The ATA risk stratification system is a reliable predictor of short-term outcomes in patients with DTC in real-world clinical settings characterized by center heterogeneity in terms of size, location, level of care, local management strategies, and resource availability.